Neurodegenerative diseases are major contributors to disability and disease. In particular, amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD) are rare nervous system disorders characterized by progressive neuronal loss and/or death. Although aging is viewed as the greatest risk factor for neurodegenerative disease, several genetic components have been discovered. For example, mutations in the copper-zinc superoxide dismutase (SOD1) gene have long been associated with ALS. Also, expanded hexanucleotide repeats of GGGGCC within a non-coding region of the C9ORF72 gene have been linked to both ALS and FTD. Currently, there is no cure for either disease, yet treatments that help to manage and/or alleviate symptoms do exist.
Inflammatory diseases include a vast variety of diseases that are often characterized by genetic mutation(s) that result in an impaired or dysfunctional immune system. Although the mechanisms of, for example, rheumatoid arthritis, inflammatory bowl disease and glomerulonephritis are not completely understood, several genetic components have been linked to the various signs and symptoms presented by patients. Such diseases are characterized by systemic inflammation and display various abnormalities throughout the patient body. As with ALS and FTD, treatments for inflammatory diseases aim only to improve symptoms and slow disease progress.
While various laboratory animal models are extensively used in the development of most therapeutics, few exist that address neurodegenerative and inflammatory diseases in ways that provide for elucidation of the exact molecular mechanism by which identified genetic components cause disease. Thus, the manner in which genetic mutations cause neurodegenerative and/or inflammatory disease remains largely unknown. Ideal animal models would contain the same genetic components and represent similar characteristics of human disease. Given the genetic differences between species, there is a high unmet need for the development of improved animal models that closely recapitulate human neurodegenerative and/or inflammatory disease. Of course, such improved animal models provide significant value in the development of effective therapeutic and/or prophylactic agents.